3 Biological Background First home work assignment: Read the first chapter (pages 1-30) of Setubal et al., (copies are available in the Taub building library, and in the central library). Answer the questions of the first assignment in the course site. Due time: (2 weeks from today). 6 Computational Biology Computational biology is the application of computational tools and techniques to (primarily) molecular biology. It enables new ways of study in life sciences, allowing analytic and predictive methodologies that support and enhance laboratory work. It is a multidisciplinary area of study that combines Biology, Computer Science, and Statistics. Computational biology is also called Bioinformatics, although many practitioners define Bioinformatics somewhat narrower by restricting the field to molecular Biology only. 7 3

6 Topics II Reconstructing evolutionary trees: Background: Darwin s theory of evolution Distance based methods (~2 weeks) Character based methods (~2 weeks) The presentations are similar to these given in the fall Semester 05-06, and can be found in the site of that semester. Updated presentations will be uploaded to the course site before the lectures. 14 Most human cells contain 46 chromosomes: Human Genome 2 sex chromosomes (X,Y): XY in males. XX in females. 22 pairs of chromosomes named autosomes. 16 6

10 The Cell All cells of an organism contain the same DNA content (and the same genes) yet there is a variety of cell types. 23 Example: Tissues in Stomach How is this variety encoded and expressed? 24 10

12 Transcription: RNA Editing 1. Transcribe to RNA 2. Eliminate introns 3. Splice (connect) exons * Alternative splicing exists Exons hold information, they are more stable during evolution. This process takes place in the nucleus. The mrna molecules diffuse through the nucleus membrane to the outer cell plasma. 27 RNA roles Messenger RNA (mrna) Encodes protein sequences. Each three nucleotide acids translate to an amino acid (the protein building block). Transfer RNA (trna) Decodes the mrna molecules to amino-acids. It connects to the mrna with one side and holds the appropriate amino acid on its other side. Ribosomal RNA (rrna) Part of the ribosome, a machine for translating mrna to proteins. It catalyzes (like enzymes) the reaction that attaches the hanging amino acid from the trna to the amino acid chain being created

13 Translation Translation is mediated by the ribosome Ribosome is a complex of protein & rrna molecules The ribosome attaches to the mrna at a translation initiation site Then ribosome moves along the mrna sequence and in the process constructs a sequence of amino acids (polypeptide) which is released and folds into a protein. 29 Genetic Code There are 20 amino acids from which proteins are build

14 Protein Structure Proteins are polypeptides of amino-acids This structure is (mostly) determined by the sequence of amino-acids that make up the protein 31 Protein Structure 32 14

15 Evolution Related organisms have similar DNA Similarity in sequences of proteins Similarity in organization of genes along the chromosomes Evolution plays a major role in biology Many mechanisms are shared across a wide range of organisms During the course of evolution existing components are adapted for new functions 33 Evolution Evolution of new organisms is driven by Diversity Different individuals carry different variants of the same basic blue print Mutations The DNA sequence can be changed due to single base changes, deletion/insertion of DNA segments, etc. Selection bias 34 15

17 Characters in Species A (discrete) character is a property which distinguishes between species (e.g. dental structure, a certain gene) A characters state is a value of the character (human dental structure). Problem: Given set of species, specified by their characters, reconstruct their evolutionary tree. 37 Species Vertices Characters Colorings States Colors Each species is identified by its states Evolutionary tree A tree with many colorings (one coloring for each character) - containing the given vertices = No teeth = teeth A B C D 38 17

18 Another tree for the same character Which tree is more reasonable? A C B D = No teeth = teeth 39 Evolutionary trees should avoid reversal transitions A species regains a state it s direct ancestor has lost. Famous (and rare) examples: Teeth in birds. Legs in snakes

19 Evolutionary trees should avoid convergence transitions Two species possess the same state while their least common ancestor possesses a different state. Famous example: The marsupials

20 Common Assumption: Characters with Reversal or Convergent transitions are highly unlikely in the Evolutionary Tree A character that exhibits neither reversals nor convergence is denoted homoplasy free. 43 A character is Homoplasy Free The corresponding coloring is convex (each color induces a connected subtree) 44 20

21 A partial coloring is convex if it can be completed to a (total) convex coloring 45 The Perfect Phylogeny Problem Input: a set of species, and many characters, each assign states (colors) to the species. Question: is there a tree T containing the species as vertices, in which all the characters (colorings) are convex? 46 21

22 The Perfect Phylogeny Problem (combinatorial setting) Input: Some colorings (C 1,,C k ) of a set of vertices (in the example: 3 colorings: left, center, right, each by (the same) two colors). RRB BBR RRR RBR Problem: Is there a tree T which includes these vertices, s.t. (T,C i ) is convex for i=1,,k? NP-Hard In general, in P for some special cases 47 22

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